Mesoscopic models of lipid bilayers and bilayers with embedded ...

7.1 Introduction 97
to reduce their hydrophobic length and thus match the thickness of the lipid bilayer
in the gel-phase [157]. Lipid-mediated protein aggregation could also occur to reduce
the stress caused by hydrophobic mismatch [145,150,158]. Domains [134] may
thus form whose functional properties differ from those of the ‘bulk’, i.e. the unperturbed
bilayer [159–161]. When the degree of mismatch is too large to be compensated
for by the adaptations just described, the proteins might partition between a
in-plane and a transmembrane orientation, or even avoid incorporation in the membrane
[156, 162, 163]. The phenomena just mentioned refer to local microscopic
changes related to mismatch adjustment. Perturbations of the membrane on the
macroscopic scale may also occur; these can range from in-plane protein segregation
and crystallization, and gel-fluid phase separation [14,147,149,164], to changes of the
three-dimensional structure of the membrane. The formation of non-bilayer phases
upon protein incorporation is an example of the latter type of phenomena [165,166].
In an effort to elucidate the effects caused at the molecular level by the lipidprotein
hydrophobic mismatch, and even their implications for the formation of biologically
relevant domain-like structures such as rafts, a number of theoretical studies
have been done with the help of different types of theoretical models [7–11, 13,
15–18, 167–171]. One of the quantities that has drawn considerable attention in the
recent years is the extension of the domain size, which is determined by the the coherence
length of the spatial fluctuations occurring in the system. Such fluctuations,
which depend on the thermodynamic state of the system, can be induced, as well as
sorted, by proteins. In the past, computer simulations have been made on a lattice
model to compute the extent of the perturbation induced by a protein on the surrounding
lipid bilayer [167]. The results from these simulations indicated that the
extension of the perturbation depends on factors such as the degree of hydrophobic
mismatch, the size of the protein (i.e. the curvature of the protein hydrophobic
surface in contact with the lipid hydrocarbon chains), and on the temperature of the
investigated system. Also, it was found that, away from the protein, the perturbation
decays in a exponential manner, and can therefore by characterized by a decay
length, ξP. This length is a coherence length which is a measure of the extension of
the range over which the lipid-mediated interaction between proteins may operate.
The decay length is also a measure of the size of small-scale inhomogeneities (i.e.
domains) experienced by proteins when embedded in the lipid bilayer. Results from
model studies of a phenomenological interfacial model for protein-like objects in a
bilayer-like system, suggest that, under well defined thermodynamic conditions, the
protein-induced perturbation may propagate without decay over a number of lipid
shells around the protein (the number of lipid shells being dependent, among others,
on the size of the protein), may extend over long ranges, and might eventually
establish a thermodynamic phase [14,15]. The phase of the multi-layered region that
the protein prefers to be surrounded with is thus said to ’wet’ the protein [14, 15].
The type of models briefly mentioned above are relatively crude (in the sense that